The field of the invention relates to Bacillus anthracis and methods for passive immunization against infection by Bacillus anthracis and treatment of infection by Bacillus anthracis. 
Bacillus anthracis is a Gram-positive, aerobic, spore-forming bacterium that causes the disease “anthrax.” There are three primary routes of infection including pulmonary (via inhalation), gastrointestinal (via ingestion), and cutaneous (via skin contact).
After infection, B. anthracis secretes a tri-partite exotoxin that includes lethal factor (LF), edema factor (EF), and protective antigen (PA). Protective antigen is synthesized as a precursor protein having an N-terminal amino acid signal sequence which is cleaved from the precursor. The processed PA then binds to a cell surface receptor, after which, PA undergoes further processing and is cleaved to release a 20 kDa fragment leaving a 63 kDa fragment bound to the cell surface. The cell surface bound 63 kDa fragment of PA multimerizes and exposes a binding site for LF and EF, which bind the PA multimer to form an exotoxin complex bound at the cell surface. This exotoxin complex then is internalized by the cell where it exerts its toxic effects. Therefore, disruption of any step in formation of the exotoxin complex may prevent the toxic effects of anthrax infection.
The threat of an anthrax outbreak, for example through bioterrorism, has increased. Although anthrax vaccines exist, their availability currently is limited. Further, these vaccines require a multiple-dose, primary vaccination schedule followed by a yearly booster. Adverse reactions at the local-injection site may deter recipients from obtaining further doses or boosters.
Treatments for anthrax infection also exist. Inhalation anthrax and gastrointestinal anthrax generally are susceptible to a spectrum of antibiotics. However, successful therapy typically requires that antibiotics be administered prior to onset of signs and symptoms of infection. Furthermore, excessive use of antibiotics selects for resistant strains of anthrax.
For these reasons, there is a critical need for alternative treatment and prevention methods for anthrax infection. Immunotherapy, optionally in conjunction with antibiotics, presents a potentially viable option for addressing the extremely high case fatality rates associated with systemic anthrax. In particular, antibodies against PA can inhibit or prevent the toxic effects of B. anthracis infection. (See, e.g., Bhatnagar et al., Critical Reviews in Microbiology 27:167-200 (2001), the content of which is incorporated by reference in its entirety). Therefore, passive immunotherapy methods that utilize compositions comprising antibodies against B. anthracis, in particular, antibodies against PA or the other exotoxins of B. anthracis, are desirable.